Monoclonal antibodies or pretargeting strategies can be used to specifically deliver radionuclides to the tumor, while sparing normal tissue. Two examples of clinical studies carried out at our department:
For renal cell carcinoma, the radiolabeled chimeric monoclonal antibody girentuximab has been extensively studied. Girentuximab specifically targets carbonic anhydrase IX (CAIX), a tumor-associated antigen ubiquitously expressed in primary ccRCC and its metastases. Because of the specific targeting of girentuximab to CAIX-expressing lesions, this antibody is a potent carrier for tumor-targeted delivery of β-emitting radionuclides. In a phase 1 clinical trial, lutetium 177 (177Lu)–girentuximab RIT proved to be safe and well tolerated. Moreover, 74% of the patients with advanced ccRCC demonstrated stable disease (SD). In a subsequent nonrandomized single-arm phase 2 study (n=14), eight patients (57%) had SD and one (7%) had a partial regression. Treatment was generally well tolerated but resulted in grade 3–4 myelotoxicity in most patients.
Monoclonal antibodies are limited by their slow blood clearance. Pretargeting with a non-radiolabelle bispecific monoclonal antibody (bsMAb) followed by a rapidly clearing radiolabeled hapten peptide improves tumour localization and lowers the radiation exposure to normal tissue. We have performed a pretargeting study in patients with the anti-CEACAM5 × anti-hapten (HSG) bsMAb, TF2, and the radiolabeled hapten-peptide, IMP288, to assess optimal pretargeting conditions and safety in patients with metastatic colorectal cancer (CRC). This phase I study demonstrated for the first time that pretargeting with bsMAb TF2 and radiolabeled IMP288 in patients with CEA-expressing CRC is feasible and safe. With this pretargeting method, tumours are specifically and rapidly targeted.
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